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| Status |
Public on Oct 10, 2014 |
| Title |
Secreted Frizzled-Related Protein 5 is Downregulated in Obesity and Promotes β-Cell Proliferation [10 days] |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Obesity is associated with an increase in β-cell mass in response to the rising demand for insulin. β-cell plasticity is essential to maintaining glucose homeostasis, however, the cellular and molecular mechanisms by which β-cell mass is regulated remain poorly understood. Recently, we described the existence of a crosstalk between the peripancreatic adipose tissue and β-cells as a novel mechanism that participates in the regulation of β-cell plasticity. Here, we identify the secreted frizzled-related protein (Sfrp) 5 as down-regulated in the pancreatic islets of obese rats as well as in the pancreatic islets of human obese patients. Our results demonstrate that the silencing of Sfrp5 induces an increase in β-cell proliferation, which we correlate with the activation of Wnt signaling and of the MAPK and PI3 kinase pathways. Together, these findings expand our understanding of the mechanisms underlying β-cell proliferation under conditions of obesity. Furthermore, this study opens new insights into the specific targeting of Sfrp5 as a novel therapeutic strategy for balancing β-cell mass.
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| Overall design |
Adult male Wistar rats (Charles River Laboratories, Wilmington, MA), 7 wk old (weighing 225–250 g), were caged individually in a 12-h light, 12-h dark cycle in a temperature- and humidity-controlled environment. Animals were divided into two dietary sets for 10 days. One group was fed with standard chow diet (supplying 8% of calories as fat; type AO4 from Panlab, Barcelona, Spain). The second group was fed with a cafeteria diet (66% of calories as fat), as previously described (Endocrinology 2012;153:177-87). Pancreatic islets were isolated through collagenase perfusion of the pancreas, Histopaque gradient and hand-picking under microscopic guidance. Ten micrograms of total RNA from islets were converted into cRNA, biotinylated, fragmented, and hybridized to GeneChip Rat Genome 230 2.0 (Affymetrix, Santa Clara, CA). Ten microarrays were hybridized, five with independent samples coming from rats fed with standard chow (lean group) and five with independent samples coming from rats fed with the cafeteria diet (obese group).
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| Contributor(s) |
Rebuffat SA, Oliveira J, Altirriba J, Palau N, Garcia A, Esteban Y, Nadal B, Gomis R |
| Citation(s) |
24006088 |
| Submission date |
Feb 04, 2013 |
| Last update date |
Jul 31, 2017 |
| Contact name |
Jordi Altirriba |
| E-mail(s) |
altirriba@hotmail.com
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| Organization name |
Centre Médical Universitaire de Genève
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| Department |
Dpts de Médecine Interne et de Physiologie cellulaire et Métabolisme
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| Lab |
Laboratoire du Métabolisme
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| Street address |
Rue Michel-Servet 1
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| City |
Genève |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE44047 |
Secreted Frizzled-Related Protein 5 is Downregulated in Obesity and Promotes β-Cell Proliferation |
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| Relations |
| BioProject |
PRJNA188421 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44045_RAW.tar |
43.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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